Proteomic Markers for ALS

ALS 蛋白质组标记

基本信息

批准号：
7492882
负责人：
Jonathan David Glass
金额：
$ 16.73万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7492882
关键词：
Achievement Address Algorithms Amyotrophic Lateral Sclerosis Animal Disease Models Animals Arts Bioinformatics Biological Markers Cerebrospinal Fluid Classification Clinic Clinical Clinical Research Data Databases Development Diagnosis Diagnostic tests Disease Disease Progression Early Diagnosis Familial Amyotrophic Lateral Sclerosis Family Functional disorder Goals Human Individual Investigation Life Methods Modeling Monitor Motor Mus Mutation Nerve Nerve Tissue Neurodegenerative Disorders Pathogenesis Pathway interactions Patients Pattern Plasma Population Process Prospective Studies Proteins Proteomics Recruitment Activity Research Sampling Sensitivity and Specificity Spinal Cord Staging Study Subject Surrogate Markers Technology Testing Tissues Transgenic Organisms Translating Translations Ventral Roots analog base day disorder prevention insight novel programs research study response success superoxide dismutase 1 tool

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research program is to discover protein biomarkers for Amyotrophic Lateral Sclerosis (ALS). Biomarkers for neurodegenerative diseases are necessary for accurate diagnosis and monitoring of disease progression and response to therapy. Biomarkers also provide important clues about mechanisms of disease pathogenesis, identifying pathways of cellular dysfunction during the course of disease. Success in biomarker discovery is greatly enhanced when investigation is focused on a homogenous disease population where there is a relevant animal model of the disease. ALS caused by mutations in superoxide dismutase 1 (SOD1-ALS) meets these criteria, and is the focus of this proposal. There are two specific aims: 1) We will use state of the art proteomic methods to quantitatively compare 3000 proteins from spinal cords and motor nerves of SOD1-ALS mice and their normal littermates. We will compare mice from presymptomatic, early symptomatic and late stages of disease in order to correlate protein patterns with the progression of disease. 2) We will select a subset of proteins (about 40) as possible candidate biomarkers based on rank order criteria, such as magnitude of change and progression of change with disease. In order to translate the proteomic findings from tissues into biomarkers that might be used in clinical practice, the selected proteins will be specifically investigated in plasma and spinal fluid samples from SOD1-ALS mice and controls. Finally, we will investigate these candidate biomarkers in plasma and spinal fluid samples from people with ALS, including those with SOD1-ALS and those with sporadic ALS. Here we will take advantage of the large clinical research database of families with ALS at the Emory ALS Center. This proposal represents a systematic approach to biomarker discovery using the most modern technology available combined with sophisticated bioinformatics. We will use these tools develop biomarkers for ALS that are essential for identifying pathogenic mechanisms and developing novel treatments. We propose to use state of the art proteomics combined with sophisticated bioinformatics to identify protein biomarkers in Amyotrophic Lateral Sclerosis (ALS). We will screen for changes in about 3000 proteins in spinal cord and nerve tissue from the SOD1-ALS mouse, and then identify a specific subset of proteins as potential biomarkers. These candidate biomarkers will be tested for their sensitivity and specificity for disease in plasma and spinal fluid samples from mice and people with ALS.

描述（由申请人提供）：该研究计划的长期目标是发现肌萎缩性侧索硬化症（ALS）的蛋白质生物标志物。为了准确诊断和监测疾病进展和对治疗的反应，需要用于神经退行性疾病的生物标志物。生物标志物还提供了有关疾病发病机理机制的重要线索，鉴定了疾病过程中细胞功能障碍的途径。当研究集中在具有相关动物模型的同质疾病人群上时，生物标志物发现的成功大大增强。由超氧化物歧化酶1（SOD1-AL）突变引起的ALS符合这些标准，这是该提案的重点。有两个具体的目的：1）我们将使用TAR TART蛋白质组学方法来定量比较SOD1-ALS小鼠的脊髓和运动神经的3000种蛋白质及其正常同窝仔。我们将比较疾病的症状，早期症状和晚期的小鼠，以便将蛋白质模式与疾病的进展相关。 2）我们将根据等级顺序标准（例如变化的幅度和随着疾病的变化进展）选择蛋白质的子集（约40个）作为候选生物标志物。为了将组织的蛋白质组学发现转化为可能在临床实践中使用的生物标志物，将在SOD1-ALS小鼠和对照组的血浆和脊髓液样品中进行特殊研究。最后，我们将研究来自ALS患者的血浆和脊髓液样品中的这些候选生物标志物，包括患有SOD1-AL的人和零星ALS的人。在这里，我们将利用Emory ALS中心拥有ALS家庭的大型临床研究数据库。该建议代表了一种使用最现代的技术与复杂的生物信息学结合使用的最现代技术的系统性发现方法。我们将使用这些工具为ALS开发生物标志物，这些ALS对于识别致病机制并开发新的治疗方法至关重要。我们建议使用艺术蛋白质组学的状态，并结合复杂的生物信息学来鉴定肌萎缩性横向硬化症（ALS）中的蛋白质生物标志物。我们将筛选从SOD1-ALS小鼠中的脊髓和神经组织中约3000种蛋白质的变化，然后将蛋白质的特定子集确定为潜在的生物标志物。这些候选生物标志物将通过小鼠和ALS患者的血浆和脊髓液样品中疾病的敏感性和特异性进行测试。